Human papillomaviruses (primarily HPV 16 and 18) play a central role in the development of in situ and invasive cervical cancer. The fact that most cervical intraepithelial lesions spontaneously resolve, along with the high costs incurred by follow-up of women with Pap smears showing atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesions (LSIL), has generated interest in the use of HPV DNA assays for managing women with cervical abnormalities. A large proportion of women in the United States do not undergo routine Pap smear screening according to recommended screening intervals, suggesting a need for an alternative, non-invasive method for cervical cancer screening. However, studies that have assessed the performance of self-collected screening methods for detection of high-grade cervical disease have been limited by generalizability, sample size, verification bias, and other methodological flaws. There has not been a large study in the United States to examine the possibility of using a self-collected sample to test for HPV DNA as screening for CIN 2/3. The long term goal of the proposed study is to evaluate whether a self-collected test for oncogenic types of HPV could be used to screen women to detect CIN 2-3. Specifically, the study will (1) estimate the accuracy (e.g., sensitivity, specificity, detection rate, and false referral rate) of HPV DNA testing using self-collected vaginal samples relative to the accuracy of clinician-directed ThinPrep Pap smears for detecting biopsy-confirmed CIN 2-3, and (2) estimate the accuracy of HPV testing of self-collected samples relative to testing of clinician-directed samples for detecting biopsy-confirmed CIN 2-3. The study will be conducted as part of the ongoing Evaluation of Cervical Cancer Screening Methodologies (EVA) project among a population of women attending Planned Parenthood of Western Washington (PPWW) clinics (Tacoma, Lakewood, and Federal Way). Approximately 2,400 women ages 18-55 will be screened throughout the course of the study. Those with (1) ASCUS, LSIL, or HSIL on Pap smear, (2) high-risk HPV DNA detected in self-administered or clinician-administered sampling, and (3) a 10% random sample of women with normal Pap smears and negative HPV DNA test results at the screening visit will be asked to return for a follow-up visit, which will include specimens for a ThinPrep smear and HPV testing and colposcopically-directed biopsy of cervical lesions. An accurate self-test for high-risk HPV types could have several important public health implications, by offering women (1) an alternative cervical screening method, (2) triage for equivocal Pap smears, (3) surveillance for recurrence after treatment for CIN 2 or higher, (4) testing for other STDs, and (5) reduced costs associated with office visits.